Quinolone--and naphthyridonecarboxylic acid derivatives

ABSTRACT

The invention relates to new quinolone- and naphthyridonecarboxylic acid derivatives which are substituted in the 7-position by a tricyclic amine radical, their salts, processes for their preparation and antibacterial compositions comprising these compounds.

This is a division of application Ser. No. 08/508,603, filed on Jul. 28,1995 now U.S. Pat. No. 5,605,910.

The invention relates to new quinolone- and naphthyridonecarboxylic acidderivatives which are substituted in the 7-position by a tricyclic amineradical, their salts, processes for their preparation and antibacterialcompositions comprising these compounds.

Quinolonecarboxylic acids which are substituted in the 7-position by abicyclic unsaturated amine radical are already known from the patentapplications EP 520 240 (Bayer) and JP 4 253 973 (Banyu). Thesecompounds are distinguished by a high antibacterial activity. However,they have the disadvantage that they have a high genotoxic potential,which renders their use as medicaments impossible. The invention istherefore based on the object of discovering compounds which show areduction in genotoxic properties, coupled with a high antibacterialactivity.

It has now been found that the compounds of the formula (I)

    T--Q                                                       (I)

in which

Q denotes a radical of the formulae ##STR1## wherein

R¹ represents alkyl which has 1 to 4 carbon atoms and is optionallymono- or disubstituted by halogen or hydroxyl, alkenyl having 2 to 4carbon atoms, cycloalkyl which has 3 to 6 carbon atoms and is optionallysubstituted by 1 or 2 fluorine atoms, bicyclo 1.1.1!-pent-1-yl,1,1-dimethylpropargyl, 3-oxetanyl, methoxy, amino, methylamino,dimethylamino or phenyl which is optionally mono- or disubstituted byhalogen, amino or hydroxyl,

R² represents hydrogen, alkyl which has 1 to 3 carbon atoms and isoptionally substituted by hydroxyl, methoxy, amino or dimethylamino,benzyl, (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl, acetoxymethyl,pivaloyloxymethyl, 5-indanyl, phthalidinyl or 3-acetoxy-2-oxo-butyl,

R⁹ represents hydrogen or alkyl which has 1 to 3 carbon atoms and isoptionally substituted by methoxy, hydroxyl or halogen,

X¹ represents halogen or nitro,

X² represents hydrogen, halogen, amino, hydroxyl, methoxy, mercapto,methyl, halogenomethyl or vinyl,

A represents N or C--R⁷, wherein

R⁷ represents hydrogen, halogen, CF₃, OCH₃, OCHF₂, CH₃, CN, CH═CH₂ orC.tbd.CH, or together with R¹ can also form a bridge having thestructure --*O--CH₂ --CH--CH₃, --*S--CH₂ --CH₂ --, --*S--CH₂ --CH--CH₃,--*S--CH₂ --CH--CH₂ F, --*CH₂ --CH₂ --CH--CH₃ or --*O--CH₂ --N--R⁸,wherein the atom labelled with * is linked to the carbon atom of A andwherein

R⁸ denotes hydrogen, methyl or formyl, and

D represents N or C--R¹⁰, wherein

R¹⁰ represents hydrogen, halogen, CF₃, OCH₃, OCHF₂ or CH₃, or togetherwith R⁹ can also form a bridge having the structure --*O--CH₂ --,--*NH--CH₂ --, --*N(CH₃)--CH₂ --, --*N(CH₃)--CH₂ --, --*N(C₂ H₅)--CH₂--, --*N(C₃ H₅)--CH₂ -- or --*S--CH₂ --, wherein the atom labelledwith * is linked to the carbon atom of D, and

T denotes a radical of the formula ##STR2## wherein

B represents NR³ R⁴ or OR⁵, wherein

R³ represents hydrogen, methyl or alkoxycarbonyl having 1 to 4 carbonatoms in the alkyl part,

R⁴ represents hydrogen or methyl and

R⁵ represents hydrogen or methyl,

R⁶ represents hydrogen or methyl,

m represents 0 or 1 and

n represents 1 or 2,

and wherein a single or a double bond can stand between the carbon atomsa and b,

and pharmaceutically usable hydrates and acid addition salts thereof, aswell as the alkali metal, alkaline earth metal, silver and guanidiniumsalts of the underlying carboxylic acids, have a high antibacterialaction, in particular against Gram-positive bacteria, coupled with agood tolerability.

Preferred compounds of the formula (I) are those

in which

Q and T have the abovementioned meaning and

R¹ represents alkyl which has 1 to 4 carbon atoms and is optionallymono- or disubstituted by halogen, alkenyl having 2 to 3 carbon atoms,cycloalkyl which has 3 or 4 carbon atoms and is optionally substitutedby 1 fluorine atom, bicyclo 1.1.1!pent-1-yl, 1,1-dimethylpropargyl,3-oxetanyl, methylamino or phenyl which is optionally mono- ordisubstituted by fluorine, amino or hydroxyl,

R² represents hydrogen, alkyl having 1 to 2 carbon atoms, benzyl or(5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl,

R⁹ represents hydrogen or alkyl which has 1 to 2 carbon atoms and isoptionally mono- to trisubstituted by fluorine,

X¹ represents fluorine or chlorine,

X² represents hydrogen, halogen, amino, methyl, trifluoromethyl orvinyl,

A represents N or C--R⁷, wherein

R⁷ represents hydrogen, halogen, CF₃, OCH₃, OCHF₂, CH₃, CN, CH═CH₂ orC.tbd.H, or together with R¹ can also form a bridge having the structure--*O--CH₂ --CH--CH₃, --*S--CH₂ --CH₂ --, --*CH₂ --CH₂ --CH--CH₃ or--*O--CH₂ --N--R⁸, wherein the atom labelled with * is linked to thecarbon atom of A, and wherein

R⁸ denotes hydrogen or methyl, and

D represents N or C--R¹⁰, wherein

R¹⁰ represents hydrogen, fluorine, chlorine, CF₃, OCH₃ or CH₃, ortogether with R⁹ can also form a bridge having the structure --O--CH₂--, --*N(CH₃)--CH₂ --, --*N(C₂ H₅)--CH₂ --, --*N(C₃ H₅)--CH₂ -- or--*S--CH₂ --, wherein the atom labelled with * is linked to the carbonatom of D, and

B represents NR³ R⁴ or OR⁵, wherein

R³ represents hydrogen, methyl or alkoxycarbonyl having 1 to 4 carbonatoms in the alkyl part,

R⁴ represents hydrogen or methyl and

R⁵ represents hydrogen or methyl,

R⁶ represents hydrogen or methyl,

m represents 0 or 1 and

n represents 1 or 2,

wherein a single or a double bond can stand between the carbon atoms aand b,

and pharmaceutically usable hydrates and acid addition salts thereof andthe alkali metal, alkaline earth metal, silver and guanidinium salts ofthe underlying carboxylic acids.

Compounds of the formula (I) which are particularly preferred are those

in which

Q and T have the abovementioned meaning and

in which

R¹ represents alkyl which has 1 to 4 carbon atoms and is optionallymono- or disubstituted by fluorine, vinyl, cyclopropyl which isoptionally substituted by 1 fluorine atom or phenyl which is optionallymono- or disubstituted by fluorine,

R² represents hydrogen, alkyl having 1 to 2 carbon atoms or(5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl,

R⁹ represents hydrogen or methyl which is optionally mono- totrisubstituted by fluorine,

X¹ represents fluorine,

X² represents hydrogen, fluorine, amino, methyl or vinyl,

A represents N or C--R⁷, wherein

R⁷ represents hydrogen, fluorine, chlorine, bromine, CF₃, OCH₃, OCHF₂,CH₃, CN, CH═CH₂ or C.tbd.CH, or together with R¹ can also form a bridgehaving the structure --*O--CH₂ --CH--CH₃ or --*O--CH₂ --N--R⁸, where theatom labelled with * is linked to the carbon atom of A, and wherein

R⁸ denotes hydrogen or methyl, and

D represents N or C--R¹⁰, wherein

R¹⁰ represents hydrogen, fluorine, chlorine or OCH₃, or together with R⁹can also form a bridge having the structure --*O--CH₂ --, --*N(CH₃)--CH₂--, --*N(C₂ H₅)--CH₂ -- or --*S--CH₂ --, wherein the atom labelledwith * is linked to the carbon atom of D, and

B represents NR³ R⁴ or OR⁵, wherein

R³ represents hydrogen or methyl,

R⁴ represents hydrogen or methyl and

R⁵ represents hydrogen or methyl,

R⁶ represents hydrogen,

m represents 0 or 1 and

n represents 1 or 2,

wherein a single or a double bond can stand between the carbon atoms aand b,

and pharmaceutically usable hydrates and acid addition salts thereof andthe alkali metal, alkaline earth metal, silver and guanidinium salts ofthe underlying carboxylic acids.

It has furthermore been found that the compounds of the formula (I) areobtained by a process in which compounds of the formula (II)

    Y--Q                                                       (II)

in which

Q has the abovementioned meaning and

Y represents halogen, in particular fluorine or chlorine,

are reacted with compounds of the formula (III) ##STR3## in which

B, R⁶, m, n, a and b have the abovementioned meanings,

if appropriate in the presence of acid-trapping agents, and anyprotective groups are split off.

If, for example,6,7-difluoro-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylicacid and 4-aza-tricyclo 5.2.1.0²,6 !dec-8-en-1-ylamine are used asstarting substances, the course of the reaction can be represented bythe following equation: ##STR4##

The compounds of the formula (II) used as starting compounds are knownor can be prepared by known methods. They can be employed either asracemic or as enantiomerically pure compounds. Examples which may bementioned are:

7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid, 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,6-chloro-1-cyclopropyl-7,8-difluoro-1,4-dihydroxo-4-oxo-3-quinolinecarboxylicacid,8-chloro-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,1-cyclopropyl-6,7,8-trifluoro-1,4dihydro-4-oxo-3-quinolinecarboxylicacid,5-bromo-1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,5-bromo-1-(2,4-difluorophenyl)-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,1-cyclopropyl-6,7-difluoro-1,4dihydro-8-methyl-4-oxo-3-quinolinecarboxylicacid, 6,7-difluoro-1-ethyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid,7-chloro-6-fluoro-1-ethyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid,7-chloro-6-fluoro-1,4-dihydro-1-(2-hydroxyethyl)-4-oxo-3-quinolinecarboxylicacid,6,7-fluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-3-quinoline-carboxylicacid,7-chloro-6-fluoro-1,4-dihydro-1-methoxy-4-oxo-3-quinolinecarboxylicacid,7-chloro-6-fluoro-1,4dihydro-1-methylamino-4-oxo-3-quinolinecarboxylicacid, 6,7-difluoro-1,4-dihydro-4-oxo-1-phenyl-3-quinolinecarboxylicacid,7-chloro-1-cyclo-propyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid, ethyl7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate,ethyl1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate,9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido- 1,2,3-de!1,4!benzoxacine -6-carboxylic acid,8,9-difluoro-6,7-dihydro-5-methyl-1-oxo-1H,5H-benzoij!-quinolicine-2-carboxylic acid,7-chloro-6-fluoro-1-phenyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid, ethyl7chloro-6-fluoro-1-(4-fluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate,6,7,8-trifluoro-1,4-dihydro-1-methylamino-4-oxo-3-quinolinecarboxylicacid, 1-amino-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,6,7,8-trifluoro-1,4-dihydro-1-dimethylamino-4-oxo-3-quinolinecarboxylicacid,6,7-difluoro-1-(4-fluorophenyl)-1,4-dihydro-8-methyl-4-oxo-3-quinolinecarboxylicacid,7-chloro-6-fluoro-1-(4-fluorophenyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,7-chloro-6-fluoro-1-(2,4fluorophenyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,6,7,8-trifluoro-1-(4-fluorophenyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,1-cyclopropyl-6,7-difluoro-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylicacid,7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-5-methyl-4-oxo-1,8-naphthyridine-3-carboxylicacid,7chloro-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-5-methyl-4-oxo-1,8-naphthyridine-3-carboxylicacid,6,7-difluoro-1,4-dihydro-1-(3-oxetanyl)-4-oxo-3-quinolinecarboxylicacid,6,7,8-trifluoro-1,4-dihydro-1-(3-oxetanyl)-4-oxo-3-quinolinecarboxylicacid, 1-(bicyclo1.1.1!pent-1-yl)-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,7-chloro-1-(1,1-dimethylpropargyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid,6,7,8-trifluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid, 6,7,8-trifluoro-1,4-dihydro-4-oxo-1-phenyl-3-quinolinecarboxylicacid,7-chloro-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid, 6,7-difluoro-1,4-dihydro-4-oxo-1-vinyl-3-quinolinecarboxylicacid,1-cyclopropyl-5,6,7,8-tetrafluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,5-amino-1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-5-hydroxy-4-oxo-3-quinolinecarboxylicacid,1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylicacid, ethyl7-chloro-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate,1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-8-vinyl-3-quinolinecarboxylicacid,1-cyclopropyl-8-ethinyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid, 9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido 1,2,3-d,e!1,3,4!benzoxadiazine-6-carboxylic acid,8-amino-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido 1,2,3-d,e!1,3,4!benzoxadiazine-6-carboxylicacid, 7,8-difluoro-5-oxo-9,1-(N-methylimino)methano!-5H-thiazolo 3,2-a!-quinoline-4-carboxylic acid,7,8-difluoro-5-oxo-9,1- (N-ethylimino)methano!-5H-thiazolo3,2-a!-quinoline-4-carboxylicacid,7,8-difluoro-5-oxo-9,1-(epoxymethano)-5H-thiazolo3,2-a!-quinoline-4-carboxylic acid,7,8-difluoro-5-oxo-9,1-(epithiomethano)-5H-thiazolo3,2-a!-quinoline-4-carboxylic acid,7,8-difluoro-1-methyl-5-oxo-5H-thiazolo 3,2-a!-quinoline-4-carboxylicacid,8-bromo-6,7-difluoro-1-(cis-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,8-chloro-6,7-difluoro-1-(cis-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,6,7-difluoro-1-(cis-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,6,7,8-trifluoro-1-(cis-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,5,6,7,8-tetrafluoro-1-(cis-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,6,7-difluoro-1-(cis-2-fluorocyclopropyl)-1,4-dihydro-8-methyl-4-oxo-3-quinolinecarboxylicacid,8-ethinyl-6,7-difluoro-1-(cis-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,6,7-difluoro-1-(cis-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-8-trifluoromethyl-3-quinolinecarboxylicacid,6,7-difluoro-1-(cis-2-fluorocyclopropyl)-8-difluoromethoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,6,7-difluoro-1-(cis-2-fluorocyclopropyl)-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylicacid,6,7-difluoro-1-(cis-2-fluorocyclopropyl)-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylicacid,5-amino-6,7,8-trifluoro-1-(cis-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid, 8-bromo-6,7-difluoro-1-(1R,2S)-2-fluorocyclopropyl!-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid, 8-chloro-6,7-difluoro-1-(1R,2S)-2-fluorocyclopropyl!-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid, 6,7-difluoro-1-(1R,2S)-2-fluorocyclopropyl!-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid, 6,7,8-trifluoro-1-(1R,2S)-2-fluorocyclopropyl!-1,4dihydro-4-oxo-3-quinolinecarboxylicacid, 5,6,7,8-tetrafluoro-1-(1R,2S)-2-fluorocyclopropyl!-1,4-dihydroxo-3-quinolinecarboxylic acid,6,7-difluoro-1-(1R,2S)-2-fluorocyclopropyl!-1,4-dihydro-8-methyl-4-oxo-3-quinolinecarboxylicacid, 8-ethinyl-6,7-difluoro-1-(1R,2S)-2-fluorocyclopropyl!-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid, 6,7-difluoro-1-(1R,2S)-2-fluorocyclopropyl!-1,4-dihydro-4-oxo-8-trifluoromethyl-3-quinolinecarboxylicacid, 6,7-difluoro-1-(1R,2S)-2-fluorocyclopropyl!-8-difluoromethoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid, 6,7-difluoro-1-(1R,2S)-2-fluorocyclopropyl!-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylicacid, 6,7-difluoro-1-(1R,2S)-2-fluorocyclopropyl!-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylicacid and 5-amino-6,7,8-trifluoro-1-(1R,2S)-2-fluorocyclopropyl!-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid.

The tricyclic amines of the formula (III) required as starting compoundsare new. They can be prepared by the methods represented in equation 1:a cyclic diene (1) is reacted with an imide (2) in the context of aDiels-Alder reaction to give, the adduct (3). The compounds (3) can bebroken down as nitrites (G═CN) or esters (G═COOC₂ H₅) via amideintermediate stages (4) to give amines (5), which can be hydrogenated,for example with complex hydrides, to give the tricyclic diamines (6).If the radical R in (6) represents benzyl, this can be split off byhydrogenolysis with simultaneous hydrogenation of the double bond toform the saturated tricyclic diamine (7). The compounds (3) withsubstituents such as, for example, G═OCH₃, OH, CN, COOC₂ H₅ or N(CH₃)₂can also be reduced directly with complex hydrides to give the compounds(8), and these can then be hydrogenated to give the saturated tricyclicdiamines (9). Selectively acylated diamines can be prepared, forexample, via tert-butoxycarbonylation of the compound (6) (R=benzyl) andsubsequent hydrogenation to give (10). Monomethylated diamines (11) or(12) can be prepared, for example, via acylation of (5) with achloroformic acid ester and subsequent reduction to give (11) or (12).The compounds (6) to (12) shown in the equation correspond to thegeneral structure (III) if R denotes H. ##STR5##

Examples which may be mentioned of tricyclic amines of the formula (III)are:

4-azatricyclo 5.2.1.0²,6 !dec-8-en-1-ylamine, 4-azatricyclo 5.2.2.0²,6!undec-8-en-1-ylamine, 4-azatricyclo 5.2.1.0²,6!dec-8-en-1-ylamine-N-carboxylic acid tert-butyl ester, 4-azatricyclo5.2.2.0²,6 !undec-8-en-1-ylamine-N-carboxylic acid tert-butyl ester,(4-azatricyclo 5.2.1.0²,6 !dec-8-en-1-yl)-methyl-amine, (4-azatricyclo5.2.2.0²,6 !undec-8-en-1-yl)-methyl-amine, (4-azatricyclo 5.2.1.0²,6!dec-8-en-1-yl)-dimethyl-amine, (4-azatricyclo 5.2.2.0²,6!undec-8-en-1-yl)-dimethyl-amine, 7-methyl-4-azatricyclo 5.2.1.0²,6!dec-8-en-1-yl-amine, 7-methyl-4-azatricyclo 5.2.2.0²,6!undec-8-en-1-yl-amine, methyl-(7-methyl-4-azatricyclo 5.2.1.0²,6!dec-8-en-1-yl)-amine, methyl-(7-methyl-4-azatricyclo 5.2.2.0²,6!undec-8-en-1-yl)-amine, dimethyl-(7-methyl-4-azatricyclo 5.2.1.0²,6!dec-8-en-1-yl)-amine, dimethyl-(7-methyl-4-azatricyclo 5.2.2.0²,6!undec-8-en-1-yl)-amine, (4-azatricyclo 5.2.1.0²,6!dec-8-en-1-yl-methyl)-amine, (4-azatricyclo 5.2.2.0²,6!undec-8-en-1-ylmethyl)amine,4-azatricyclo- 5.2.1.0²,6 !dec-8-en-1-ol,4-tricyclo 5.2.2.0²,6 !undec-8-en-1-ol, (4-azatricyclo- 5.2.1.0²,6!dec-8-en-1-yl)-methanol, (4-azatricyclo 5.2.2.0²,6!undec-8-en-1-yl)-methanol, 4-azatricyclo 5.2.1.0²,6 !dec-1-ylamine,4-azatricyclo 5.2.2.0²,6 !undec-1-ylamine, tert-butyl 4-azatricyclo5.2.1.0²,6 !dec-1-ylamine-N-carboxylate, tert-butyl 4-azatricyclo5.2.2.0²,6 !undec-1-ylamine-N-carboxylate, (4-azatricyclo 5.2.1.0²,6!dec-1-yl)-methyl-amine, (4-azatricyclo 5.2.2.0²,6!undec-1-yl)-methyl-amine, (4-azatricyclo 5.2.1.0²,6!dec-1-yl)-dimethyl-amine, (4-azatricyclo 5.2.2.0²,6!undec-1-yl)-dimethyl-amine, 7-methyl-4-azatricyclo 5.2.1.0²,6!dec-1-yl-amine, 7-methyl-4-azatricyclo 5.2.2.0²,6!undec-1-yl-amine,methyl-(7-methyl-4-azatricyclo 5.2.1.0²,6!dec-1-yl)-amine, methyl-(7-methyl-4-azatricyclo 5.2.2.0²,6!undec-1-yl)-amine, dimethyl-(7-methyl-4-azatricyclo 5.2.1.0²,6 !dec-1-yl)-amine, dimethyl-(7-methyl-4-azatricyclo 5.2.2.0²,6!undec-1-yl)-amine, (4-azatricyclo 5.2.1.0²,6 !dec-1-ylmethyl)amine,(4-azatricyclo 5.2.2.0²,6 !undec-1-yl-methyl)amine, 4-azatricyclo5.2.1.0²,6 !dec-1-ol, 4-azatricyclo 5.2.2.0²,6 !undec-1-ol,(4-azatricyclo 5.2.1.0²,6 !dec-1-yl)-methanol and (4-azatricyclo5.2.2.0²,6 !undec-1-yl)-methanol.

The enantiomerically pure compounds of the formula (III) used asstarting compounds can be prepared by the following processes:

1. The racemic tricyclic amines (III) can be reacted withenantiomerically pure acids, for example carboxylic acids or sulphonicacids, such as N-acetyl-L-glutamic acid, N-benzoyl-L-alanine,3-bromo-camphor-9-sulphonic acid, camphor-3-carboxylic acid, cis-camphoracid, camphor-10-sulphonic acid, O,O'-dibenzoyl-tartaric acid, D- orL-tartaric acid, mandelic acid, α-methoxy-phenylacetic acid,1-phenyl-ethanesulphonic acid or α-phenyl-succinic acid, to give amixture of the diastereomeric salts, which can be separated into thediastereomerically pure salts by fractional crystallization (see P.Newman, Optical Resolution Procedures for Chemical Compounds, Volume 1).The enantiomerically pure amines can be liberated by treatment of thesesalts with alkali metal hydroxides or alkaline earth metal hydroxides.

2. In a manner similar to that described under 1., splitting ofracemates of the basic intermediate stages which occur duringpreparation of the racemic dicyclic amines can be carried out with theabovementioned enantiomerically pure acids. Examples of such basicintermediate stages are compounds having the structure (5) in equation1.

3. Both the racemic amines (III) and the intermediate stages in theirpreparation, such as, for example, compounds having the structures (3)to (5) in equation 1, can be separated by chromatography over chiralcarrier materials, if appropriate after acylation (see, for example, G.Blaschke, Angew. Chem. 92, 14 1980!).

4. Both the racemic amines (III) and basic intermediate stages, such as,for example, compounds having the structure (5) in equation 1, can beconverted by chemical linking to chiral acyl radicals into diastereomermixtures, which can be separated by distillation, crystallization orchromatography into the diastereomerically pure acyl derivatives, fromwhich the enantiomerically pure amines can be isolated by hydrolysis.Examples of reagents for linking with chiral acyl radicals are:α-methoxy-α-trifluoromethyl-phenylacetyl chloride, menthyl isocyanate,D- or L-α-phenyl-ethyl isocyanate, menthyl chloroformate andcamphor-10-sulphonyl chloride.

5. In the course of the synthesis of the tricyclic amines (III), chiralprotective groups can also be introduced instead of achiral protectivegroups. Diastereomers which can be separated are obtained in thismanner. For example, in the synthesis of the compound (3) in equation 1,the benzyl radical can be replaced by the α-phenylethyl radical havingthe R or S configuration.

The reaction of (II) with (III), in which the compounds (III) can alsobe employed in the form of their salts, such as, for example, thehydrochlorides, is preferably carried out in a diluent, such as dimethylsulphoxide, N,N-dimethylformamide, N-methylpyrrolidone,hexamethyl-phosphoric acid trisamide, sulpholane, acetonitrile, water,an alcohol, such as methanol, ethanol, n-propanol, isopropanol or glycolmonomethyl ether, or pyridine. Mixtures of these diluents can also beused.

Acid-binding agents which can be used are all the customary inorganicand organic acid-binding agents. These include, preferably, the alkalimetal hydroxides, alkali metal carbonates, organic amines and amidines.Specific agents which may be mentioned as particularly suitable are:triethylamine, 1,4-diazabicyclo 2.2.2!octane (DABCO), 1,8-diazabicyclo5.4.0!undec-7-ene (DBU) or excess amine (III).

The reaction temperatures can be varied within a relatively wide range.In general, the reaction is carried out at between about 20° and 200°C., preferably between 80° and 160° C.

The reaction can be carried out under normal pressure, but also underincreased pressure. In general, it is carried out under pressures ofbetween about 1 and 100 bar, preferably between 1 and 10 bar.

In carrying out the process according to the invention, 1 to 15 mol,preferably 1 to 5 mol, of the compound (III) are employed per mole ofcompound (II).

Free amino groups can be protected by a suitable amino protective group,such as, for example, by the tert-butoxycarbonyl radical or anazomethine protective group, during the reaction and liberated againwhen the reaction has ended.

To prepare the esters according to the invention, the underlyingcarboxylic acid is preferably reacted in excess alcohol in the presenceof strong acids, such as sulphuric acid, anhydrous hydrogen chloride,methanesulphonic acid, p-toluenesulphonic acid or acid ion exchangers,at temperatures of about 20° to 1 80° C., preferably about 60° to 120°C. The water of reaction formed can also be removed by azeotropicdistillation with chloroform, carbon tetrachloride or toluene.

The esters can also advantageously be prepared by heating the underlyingacid with dimethylformamide dialkyl acetal in a solvent, such asdimethylformamide.

The esters used as prodrugs, such as, for example, the(5-methyl-2-oxo-1,3-dioxol-4-yl-methyl) ester, are obtained by reactingan alkali metal salt of the underlying carboxylic acid, which canoptionally be protected by a protective group on the N atom, with4-bromomethyl- or 4-chloromethyl-5-methyl-1,3-dioxol-2-one in a solvent,such as dimethylformamide, dimethylacetamide, N-methyl-pyrolidone,dimethyl sulphoxide or tetramethylurea, at temperatures of about 0° to100° C., preferably 0° to 50° C.

The acid addition salts of the compounds according to the invention areprepared in the customary manner, for example by dissolving in excessaqueous acid and precipitating the salt with a water-miscible solvent,such as methanol, ethanol, acetone or acetonitrile. It is also possibleto heat an equivalent amount of betaine and acid in water or an alcohol,such as glycol monomethyl ether, and then to evaporate the mixture todryness or to filter off the precipitated salt with suction.Pharmaceutically usable salts are to be understood as meaning, forexample, the salts of hydrochloric acid, sulphuric acid, acetic acid,glycolic acid, lactic acid, succinic acid, citric acid, tartaric acid,2-hydroxyglutaric acid, methanesulphonic acid, 4-toluenesulphonic acid,galacturonic acid, glucuronic acid, 5-oxotetrahydrofuran-2-carboxylicacid, embonic acid, glutamic acid or aspartic acid.

The alkali metal and alkaline earth metal salts of the carboxylic acidsaccording to the invention are obtained, for example, by dissolving thebetaine in excess alkali metal hydroxide solution or alkaline earthmetal hydroxide solution, filtration to remove the undissolved betaineand evaporation of the filtrate to dryness. The sodium, potassium andcalcium salts are pharmaceutically suitable. The corresponding silversalts are obtained by reaction of an alkali metal salt or alkaline earthmetal salt with a suitable silver salt, such as silver nitrate.

In addition to the active compounds mentioned in the examples, theactive compounds mentioned below and those listed in Tables 1 to 8 canalso be prepared, and can exist either as racemates or asenantiomerically pure compounds, or else where appropriate asdiastereomer mixtures or as diastereomerically pure compounds:

8-(1-amino-4-azatricyclo 5.2.1.0²,6!dec-8-en-4-yl)-7-fluoro-5-oxo-9,1-(epoxymethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid, 8-(1-methylamino-4-azatricyclo5.2.1.0²,6 !dec-8en-4-yl)-7-fluoro-5-oxo-9,1-(epoxymethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid, 8-(1-amino-7-methyl-4-azatricyclo5.2.1.0²,6 !dec-8-en-4-yl)-7-fluoro-5-oxo-9,1-(epoxymethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid, 8-(1-aminoazatricyclo 5.2.1.0²,6!dec-4-yl)-7-fluoro-5-oxo-9,1-(epoxymethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid, 8-(1-methylamino-4-azatricyclo5.2.1.0²,6 !dec-4-yl)-7-fluoro-5-oxo-9,1-(epoxymethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid, 8-(1-amino-7-methyl-4-azatricyclo5.2.1.0²,6 !dec-4-yl)-7-fluoro-5-oxo-9,1-(epoxymethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid, 8-(1-amino-4-azatricyclo 5.2.1.0²,6!dec-8-en-4-yl)-7-fluoro-5-oxo-9,1- (N-methylimino)methano!-5H-thiazolo3,2-a!quinoline-4-carboxylic acid, 8-(1-methylamino-4-azatricyclo5.2.1.0²,6 !dec-8-en-4-yl)-7-fluoro-5-oxo-9,1-(N-methyl-imino)methano!-5H-thiazolo 3,2-a!quinoline-4-carboxylic acid,8-(1-amino-7-methyl-4-azatricyclo 5.2.1.0²,6!dec-8-en-4-yl)-7-fluoro-5-oxo-9,1- (N-methyl-imino)methano!-5H-thiazolo3,2-a!quinoline-4-carboxylicacid, 8-(1-amino-4-azatricyclo 5.2.1.0²,6!dec-4-yl)-7-fluoro-5-oxo-9,1- (N-methyl-imino)methano!-5H-thiazolo3,2-a!quinoline-4-carboxylic acid, 8-(1-methylamino-4-azatricyclo5.2.1.0²,6 !dec-4-yl)-7-fluoro-5-oxo-9,1-(N-methyl-imino)methano!-5H-thiazolo 3,2-a!quinoline-4-carboxylic acid,8-(1-amino-7-methyl-4-azatricyclo 5.2.1.0²,6!dec-4-yl)-7-fluoro-5-oxo-9,1- (N-methyl-imino)methano!-5H-thiazolo3,2-a!quinoline-4-carboxylic acid, 8-amino-10-(1-amino-4-azatricyclo5.2.1.0²,6 !decan-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido1,2,3-d,e! 1,3,4!benzoxadiazine-6-carboxylic acid,10-(1-amino-4-azatricyclo- 5.2.1.0²,6!decan-4-yl)-9-fluoro3-methyl-7-oxo-2,3-dihydro-7H-pyrido 1,2,3-d,e!-1,3,4!benzoxadiazine-6-carboxylic acid,10-(1-amino-7-methyl-4-azatricyclo 5.2.1.0²,6!decan-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido 1,2,3-d,e!1,3,4!benzoxadiazine-6-carboxylicacid, 10-(1-methylamino-4-azatricyclo5.2.1.0²,6 !decan-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido1,2,3-d,e! 1,3,4!-benzoxadiazine-6-carboxylic acid,10-(1-amino-4-azatricyclo 5.2.1.0²,6!dec-8-en-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido 1,2,3-d,e!1,3,4!benzoxadiazine-6-carboxylic acid, 10-(1-methylamino-4-azatricyclo5.2.1.0²,6 !dec-8-en-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido1,2,3-d,e! 1,3,4!benzoxadiazine-6-carboxylic acid,10-(1-amino-7-methyl-4-azatricyclo 5.2.1.0²,6!dec-8-en-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido 1,2,3-d,e!1,3,4!benzoxadiazine-6-carboxylic acid, 10-(1-amino-4-azatricyclo5.2.2.0²,6!undec-8-en-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido1,2,3-d,e! 1,4!benzoxazine-6-carboxylic acid, 10-(1-amino-4-azatricyclo5.2.2.0²,6 !undecan-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido1,2,3d,e! 1,3,4!benzoxadiazine-6-carboxylic acid,8-amino-10-(1-amino-4-azatricyclo 5.2.1.0²,6!decan-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido 1,2,3-d,e!1,4!benzoxazine-6-carboxylic acid, 10-(1-amino-4-azatricyclo 5.2.1.0²,6!decan-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido 1,2,3-d,e!1,4!benzoxazine-6-carboxylic acid, 10-(1-amino-7-methyl-4-azatricyclo5.2.1.0²,6 !decan-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido1,2,3-d,e! 1,4!benzoxazine-6-carboxylic acid,10-(1-methylamino-4-azatricyclo 5.2.1.0²,6!decan-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido 1,2,3-d,e!1,3,4!benzoxadiazine-6-carboxylic acid, 10-(1-amino-4-azatricyclo5.2.1.0²,6 !dec-8-en-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido1,2,3-d,e! 1,4!benzoxazine-6-carboxylic acid,10-(1-methylamino-4-azatricyclo 5.2.1.0²,6!dec-8-en-4-yl)-9-fluoro-3-methyl-7-oxo-2,3dihydro-7H-pyrido 1,2,3-d,e!1,4!benzoxazine-6-carboxylic acid, 10-(1-amino-7-methyl-4-azatricyclo5.2.1.0²,6 !dec-8-en-4-yl)-9-fluoro-3-methyl-7-oxo-2,3dihydro-7H-pyrido1,2,3-d,e! 1,4!benzoxazine-6-carboxylic acid,8-(1-aminomethyl-4-azatricyclo 5.2.1.0²,6!dec-4-yl)-7-fluoro-5-oxo-9,1-(epoxymethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid, 8-(1-aminomethyl-4-azatricyclo5.2.2.0²,6 !undec-4-yl)-7-fluoro-5-oxo-9,1-(epoxymethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid, 8-(1-aminomethyl-4-azatricyclo5.2.1.0²,6 !dec-8-en-4-yl)-7-fluoro-5-oxo-9,1-(epoxymethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid, 8-(1-aminomethyl-4-azatricyclo5.2.2.0²,6!undec-8-en-4-yl)-7-fluoro-5-oxo-9,1-(epoxymethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid, 8-(1-aminomethyl-4-azatricyclo5.2.1.0²,6 !dec-4-yl)-7-fluoro-5-oxo-9,1-(N-methyl-imino)methano!-5H-thiazolo 3,2-a!quinoline-4-carboxylic acid,8-(1-aminomethyl-4-azatricyclo 5.2.2.0²,6!undec-4-yl)-7-fluoro-5-oxo-9,1- (N-methyl-imino)methano!-5H-thiazolo3,2-a!quinoline-4-carboxylic acid, 8-(1-aminomethyl-4-azatricyclo5.2.1.0².6 !dec-8-en-4-yl)-7-fluoro-5-oxo-9,1-(N-methyl-imino)methano!-5H-thiazolo 3,2-a!quinoline-4-carboxylic acid,8-(1-aminomethyl-4-azatricyclo 5.2.2.0²,6!undec-8-en-4-yl)-7-fluoro-5-oxo-9,1-(N-methyl-imino)methano!-5H-thiazolo 3,2-a!quinoline-4-carboxylic acid,10-(1-aminomethyl-4-azatricyclo 5.2.1.0²,6!dec-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido 1,2,3-d,e!1,3,4!benzoxadiazine-6-carboxylic acid, 10-(1-aminomethyl-4-azatricyclo5.2.2.0²,6 !undec-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido1,2,3-d,e! 1,3,4!benzoxadiazine-6-carboxylic acid,10-(1-aminomethyl-4-azatricyclo 5.2.1.0²,6!dec-8-en-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido 1,2,3-d,e!1,3,4!benzoxadiazine-6-carboxylic acid and10-(1-aminomethyl-4-azatricyclo 5.2.2.0²,6!undec-8-en-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido1,2,3-d,e! 1,3,4!benzoxadiazine-6-carboxylic acid.

                  TABLE 1                                                         ______________________________________                                         ##STR6##                                                                     T*         A           X.sup.2    R.sup.2                                     ______________________________________                                        T.sup.I    CH          H          H                                           T.sup.I    CF          H          H                                           T.sup.I    CCl         H          H                                           T.sup.I    CCH.sub.3   H          H                                           T.sup.I    COCH.sub.3  H          H                                           T.sup.I    N           H          H                                           T.sup.I    CF          F          H                                           T.sup.I    CF          NH.sub.2   H                                           T.sup.I    CF          H          C.sub.2 H.sub.5                             T.sup.I    CCl         H          C.sub.2 H.sub.5                             T.sup.II   CH          H          H                                           T.sup.II   CF          H          H                                           T.sup.II   CCl         H          H                                           T.sup.II   CCH.sub.3   H          H                                           T.sup.II   COCH.sub.3  H          H                                           T.sup.II   N           H          H                                           T.sup.II   CF          F          H                                           ______________________________________                                         *T.sup.I = 1Amino-4-aza-tricyclo 5.2.1.0.sup.2,6 !dec 8en-4-yl                T.sup.II = 7Methyl-1-amino-4-aza-tricyclo 5.2.1.0.sup.2,6 !dec 8en-4-yl  

                  TABLE 2                                                         ______________________________________                                         ##STR7##                                                                     T*         A           X.sup.2    R.sup.2                                     ______________________________________                                        T.sup.III  CH          H          H                                           T.sup.III  CF          H          H                                           T.sup.III  CCl         H          H                                           T.sup.III  CCH.sub.3   H          H                                           T.sup.III  COCH.sub.3  H          H                                           T.sup.III  N           H          H                                           T.sup.III  CF          F          H                                           T.sup.III  CF          NH.sub.2   H                                           T.sup.III  CF          H          C.sub.2 H.sub.5                             T.sup.III  CCl         H          C.sub.2 H.sub.5                             T.sup.IV   CH          H          H                                           T.sup.IV   CF          H          H                                           T.sup.IV   CCl         H          H                                           T.sup.IV   CCH.sub.3   H          H                                           T.sup.IV   COCH.sub.3  H          H                                           T.sup.IV   N           H          H                                           T.sup.IV   CF          F          H                                           ______________________________________                                         *T.sup.III = 1Methylamino-4-aza-tricyclo 5.2.1.0.sup.2,6 !dec 8en-4-yl        T.sup.IV = 1Aminomethyl-4-aza-tricyclo 5.2.1.0.sup.2,6 !dec 8en-4-yl     

                  TABLE 3                                                         ______________________________________                                         ##STR8##                                                                     T*         A           X.sup.2    R.sup.2                                     ______________________________________                                        T.sup.V    CH          H          H                                           T.sup.V    CF          H          H                                           T.sup.V    CCl         H          H                                           T.sup.V    CCH.sub.3   H          H                                           T.sup.V    COCH.sub.3  H          H                                           T.sup.V    N           H          H                                           T.sup.V    CF          F          H                                           T.sup.V    CF          NH.sub.2   H                                           T.sup.V    CF          H          C.sub.2 H.sub.5                             T.sup.V    CCl         H          C.sub.2 H.sub.5                             T.sup.IV   CH          H          H                                           T.sup.IV   CF          H          H                                           T.sup.IV   CCl         H          H                                           T.sup.IV   CCH.sub.3   H          H                                           T.sup.IV   COCH.sub.3  H          H                                           T.sup.IV   N           H          H                                           T.sup.IV   CF          F          H                                           ______________________________________                                         *T.sup.V = 1Amino-4-aza-tricyclo 5.2.1.0.sup.2,6 !undec 8en-4-yl              T.sup.VI = 1Amino-4-aza-tricyclo 5.2.1.0.sup.2,6 !dec 4yl                

                  TABLE 4                                                         ______________________________________                                         ##STR9##                                                                     T*         A           X.sup.2    R.sup.2                                     ______________________________________                                        T.sup.VII  CH          H          H                                           T.sup.VII  CF          H          H                                           T.sup.VII  CCl         H          H                                           T.sup.VII  CCH.sub.3   H          H                                           T.sup.VII  COCH.sub.3  H          H                                           T.sup.VII  N           H          H                                           T.sup.VII  CF          F          H                                           T.sup.VII  CF          NH.sub.2   H                                           T.sup.VII  CF          H          C.sub.2 H.sub.5                             T.sup.VII  CCl         H          C.sub.2 H.sub.5                             T.sup.VIII CH          H          H                                           T.sup.VIII CF          H          H                                           T.sup.VIII CCl         H          H                                           T.sup.VIII CCH.sub.3   H          H                                           T.sup.VIII COCH.sub.3  H          H                                           T.sup.VIII N           H          H                                           T.sup.VIII CF          F          H                                           ______________________________________                                         *T.sup.VII = 1Amino-4-aza-tricyclo 5.2.1.0.sup.2,6 !undec 4yl                 T.sup.VIII = 1Methylamino-4-aza-tricyclo 5.2.1.0.sup.2,6 !dec 4yl        

                  TABLE 5                                                         ______________________________________                                         ##STR10##                                                                    T*         A           X.sup.2    R.sup.2                                     ______________________________________                                        T.sup.I    CH          H          H                                           T.sup.I    CF          H          H                                           T.sup.I    CCl         H          H                                           T.sup.I    CCH.sub.3   H          H                                           T.sup.I    COCH.sub.3  H          H                                           T.sup.I    N           H          H                                           T.sup.I    CF          F          H                                           T.sup.I    CF          NH.sub.2   H                                           T.sup.I    CF          H          C.sub.2 H.sub.5                             T.sup.I    CCl         H          C.sub.2 H.sub.5                             T.sup.I    CC CH       H          H                                           T.sup.I    CCHCH.sub.2 H          H                                           T.sup.I    COCHF.sub.2 H          H                                           T.sup.V    CCH.sub.3   H          H                                           T.sup.V    CF          H          H                                           T.sup.V    CF          NH.sub.2   H                                           T.sup.V    N           H          H                                           ______________________________________                                         *T.sup.I = 1Amino-4-aza-tricyclo 5.2.1.0.sup.2,6 !dec 8en-4-yl                T.sup.V = 1Amino-4-aza-tricyclo 5.2.2.0.sup.2,6 !undec 8en-4-yl          

                  TABLE 6                                                         ______________________________________                                         ##STR11##                                                                    T*     A          X.sup.2 R.sup.1      R.sup.2                                ______________________________________                                        T.sup.I                                                                              CH         H       C(CH.sub.3).sub.3                                                                          H                                      T.sup.V                                                                              N          H       C(CH.sub.3).sub.3                                                                          H                                      T.sup.I                                                                              N          H       C(CH.sub.3).sub.3                                                                          H                                      T.sup.V                                                                              N          CH.sub.3                                                                              C(CH.sub.3).sub.3                                                                          H                                      T.sup.V                                                                              CF         H       C(CH.sub.3).sub.3                                                                          H                                      T.sup.I                                                                              CH         H       Fluoro-tert-butyl                                                                          H                                      T.sup.V                                                                              CH         H       Fluoro-tert-butyl                                                                          H                                      T.sup.I                                                                              N          H       Fluoro-tert-butyl                                                                          H                                      T.sup.V                                                                              N          H       Fluoro-tert-butyl                                                                          H                                      T.sup.V                                                                              COCH.sub.3 H       Fluoro-tert-butyl                                                                          H                                      T.sup.I                                                                              CH         H       2,4-Difluorophenyl                                                                         H                                      T.sup.V                                                                              CH         H       2,4-Difluorophenyl                                                                         H                                      T.sup.I                                                                              CF         H       2,4-Difluorophenyl                                                                         H                                      T.sup.V                                                                              CF         H       2,4-Difluorophenyl                                                                         H                                      T.sup.I                                                                              N          H       2,4-Difluorophenyl                                                                         H                                      T.sup.V                                                                              N          H       2,4-Difluorophenyl                                                                         H                                      T.sup.V                                                                              N          H       2,4-Difluorophenyl                                                                         C.sub.2 H.sub.5                        ______________________________________                                         *T.sup.I = 1Amino-4-aza-tricyclo 5.2.1.0.sup.2,6 !dec 8en-4-yl                T.sup.V = 1Amino-4-aza-tricyclo 5.2.2.0.sup.2,6 !undec 8en-4-yl          

                  TABLE 7                                                         ______________________________________                                         ##STR12##                                                                    T*     A         X.sup.2 R.sup.1       R.sup.2                                ______________________________________                                        T.sup.I                                                                              CH        H       Bicyclo 1.1.1!pent-1-yl                                                                     H                                      T.sup.V                                                                              CH        H       Bicyclo 1.1.1!pent-1-yl                                                                     H                                      T.sup.I                                                                              N         H       Bicyclo 1.1.1!pent-1-yl                                                                     H                                      T.sup.V                                                                              N         CH.sub.3                                                                              Bicyclo 1.1.1!pent-1-yl                                                                     H                                      T.sup.I                                                                              CF        H       Bicyclo 1.1.1!pent-1-yl                                                                     H                                      T.sup.V                                                                              CF        H       Bicyclo 1.1.1!pent-1-yl                                                                     H                                      T.sup.I                                                                              COCH.sub.3                                                                              H       Bicyclo 1.1.1!pent-1-yl                                                                     H                                      T.sup.V                                                                              CCCH.sub.3                                                                              H       Bicyclo 1.1.1!pent-1-yl                                                                     H                                      T.sup.I                                                                              CH        H       3-Oxetanyl    H                                      T.sup.V                                                                              CH        H       3-Oxetanyl    H                                      T.sup.I                                                                              N         H       3-Oxetanyl    H                                      T.sup.V                                                                              N         H       3-Oxetanyl    H                                      T.sup.I                                                                              CF        H       3-Oxetanyl    H                                      T.sup.V                                                                              CF        H       3-Oxetanyl    H                                      T.sup.I                                                                              COCH.sub.3                                                                              H       3-Oxetanyl    H                                      T.sup.V                                                                              COCH.sub.3                                                                              H       3-Oxetanyl    H                                      T.sup.V                                                                              CH        H       4-Fluorophenyl                                                                              C.sub.2 H.sub.5                        ______________________________________                                         *T.sup.I = 1Amino-4-aza-tricyclo 5.2.1.0.sup.2,6 !dec 8en-4-yl                T.sup.V = 1Amino-4-aza-tricyclo 5.2.2.0.sup.2,6 !undec 8en-4-yl          

                                      TABLE 8                                     __________________________________________________________________________     ##STR13##                                                                    T* A     X.sup.2                                                                          R.sup.1 R.sup.2                                                   __________________________________________________________________________    T.sup.I                                                                          COCH.sub.3                                                                          H  CH.sub.2 CH.sub.2 F                                                                   H                                                         T.sup.V                                                                          COCH.sub.3                                                                          H  CH.sub.2 CH.sub.2 F                                                                   H                                                         T.sup.I                                                                          COCH.sub.3                                                                          H  CHCH.sub.2                                                                            H                                                         T.sup.V                                                                          COCH.sub.3                                                                          H  CHCH.sub.2                                                                            H                                                         T.sup.I                                                                          COCH.sub.3                                                                          H  4-Fluoro-                                                                             H                                                                     phenyl                                                            T.sup.V                                                                          COCH.sub.3                                                                          H  4-Fluoro-                                                                             H                                                                     phenyl                                                            T.sup.I                                                                          COCH.sub.3                                                                          H  Cyclopropyl                                                                           (5-Methyl-2-oxo-1,3-dioxol-4-yl)-methyl                   T.sup.V                                                                          COCH.sub.3                                                                          H  Cyclopropyl                                                                           (5-Methyl-2-oxo-1,3-dioxol-4-yl)-methyl                   T.sup.I                                                                          CH    H  Cyclopropyl                                                                           (5-Methyl-2-oxo-1,3-dioxol-4-yl)-methyl                   T.sup.V                                                                          CH    H  Cyclopropyl                                                                           (5-Methyl-2-oxo-1,3-dioxol-4-yl)-methyl                   T.sup.I                                                                          CF    H  Cyclopropyl                                                                           (5-Methyl-2-oxo-1,3-dioxol-4-yl)-methyl                   T.sup.V                                                                          CF    H  Cyclopropyl                                                                           (5-Methyl-2-oxo-1,3-dioxol-4-yl)-methyl                   T.sup.V                                                                          COCH.sub.3                                                                          H  Cyclopropyl                                                                           Acetoxymethyl                                             T.sup.V                                                                          COCH.sub.3                                                                          H  Cyclopropyl                                                                           Pivaloyloxymethyl                                         T.sup.V                                                                          COCH.sub.3                                                                          H  1,1-Dimethyl-                                                                         H                                                                     propargyl                                                         T.sup.V                                                                          COCH.sub.3                                                                          H  Methylamino                                                                           H                                                         T.sup.V                                                                          CH    H  tert-Butyl                                                                            (5-Methyl-2-oxo-1,3-dioxol-4-yl)-methyl                   __________________________________________________________________________     *T.sup.I = 1Amino-4-aza-tricyclo 5.2.1.0.sup.2,6 !dec 8en-4-yl                T.sup.V = 1Amino-4-aza-tricyclo 5.2.2.0.sup.2,6 !undec 8en-4-yl          

The compounds according to the invention have a potent antibiotic actionand display a broad antibacterial spectrum against Gram-positive andGram-negative germs, above all including those which are resistant tovarious antibiotics, such as, for example, penicillins, cephalosporins,aminoglycosides, sulphonamides, tetracyclines and against commerciallyavailable quinolones, coupled with a low toxicity.

These valuable properties enable them to be used as chemotherapeuticactive compounds in medicine and as substances for the preservation ofinorganic and organic materials, for example polymers, lubricants,paints, fibres, leather, paper and wood, and of foodstuffs and water.

The compounds according to the invention are active against a very broadspectrum of microorganisms. Gram-negative and Gram-positive bacteria andbacteria-like microorganisms can be combated and the diseases caused bythese pathogens can be prevented, alleviated and/or cured with the aidof these compounds.

The compounds according to the invention are distinguished by anintensified action against dormant germs. The compounds have a potentbactericidal action on dormant bacteria, that is to say bacteria whichshow no detectable growth. This relates not only to the amount to beemployed, but also to the rate of destruction. Such results have beenfound on Gram-positive and Gram-negative bacteria, in particular onStaphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis andEscherichia coli.

The compounds according to the invention are particularly active againsttypical and atypical Mycobacteria and Helicobacter pylon, and alsoagainst bacteria-like microorganisms, such as, for example, Mycoplasmaand Rickettsia. They are therefore particularly suitable in human andveterinary medicine for the prophylaxis and chemotherapy of local andsystemic infections caused by these pathogens.

The compounds are furthermore particularly suitable for combatingprotozoonoses and helminthoses.

The compounds according to the invention can be used in variouspharmaceutical formulations. Preferred pharmaceutical formulations whichmay be mentioned are tablets, coated tablets, capsules, pills, granules,suppositories, solutions, suspensions and emulsions, pastes, ointments,gels, creams, lotions, powders and sprays.

The compounds according to the invention can also be linked to β-lactamderivatives, such as, for example, cephalosporins or penems, by covalentbonds to give so-called dual action derivatives.

The following Tables 1 and 2 show the minimum inhibitory concentrationsas a measure of the antibacterial activity and the ID₅₀ values as ameasure of the genotoxic potential of a substance both for compoundsaccording to the invention and for reference compounds from the priorart (EP 520 240).

The minimum inhibitory concentrations (MIC) were determined by a seriesdilution method on Iso-Sensitest agar (Oxoid). For each test substance,a series of agar plates each comprising concentrations of the activecompound decreasing by double dilution in each case was prepared. Theagar plates were inoculated with a multipoint inoculator (Denley).Overnight cultures of the pathogens which had been diluted beforehandsuch that each inoculation point comprised about 10⁴ colony-formingparticles were used for the inoculation. The inoculated agar plates wereincubated at 37° C. and the germ growth was read off after about 20hours. The MIC value (μg/ml) indicates the lowest active compoundconcentration at which no growth was detectable with the naked eye.

The compounds according to the invention are distinguished in particularby the fact that they have lower interactions with mammalian DNAcompared with the compounds according to the prior art. The ID₅₀ isunderstood as meaning the concentration of a substance at which DNAsynthesis in cells from ovaries of the Chinese hamster (CHO-KI) isinhibited by 50%. This value is determined after incubation of thecorresponding substances in decreasing dilution stages over definedperiods of time. For this, the DNA synthesis in CHO-KI cells isdetermined in comparison with controls by means of fluorophotometricmethods.

                                      TABLE 1                                     __________________________________________________________________________    MIC values (μg/ml) and ID.sub.50 values of active compounds according      to the invention                                                                          Example                                                           Species                                                                              Strain                                                                             1  2  3  5  6  18 19 20 21 22                                     __________________________________________________________________________    E. coli                                                                              Neumann                                                                            0.125                                                                            0.015                                                                            0.015                                                                            0.015                                                                            0.06                                                                             0.03                                                                             0.03                                                                             0.03                                                                             0.015                                                                            0.125                                  Staph. aureus                                                                        133  0.662                                                                            0.015                                                                            0.015                                                                            0.015                                                                            0.015                                                                            0.015                                                                            0.015                                                                            0.015                                                                            0.015                                                                            0.031                                  Staph. aureus                                                                        ICB  8  0.062                                                                            0.031                                                                            0.031                                                                            0.125                                                                            0.25                                                                             0.06                                                                             0.125                                                                            0.125                                                                            2                                             25701                                                                  Ps. aeru-                                                                            Walter                                                                             8  0.5                                                                              0.5                                                                              1  4  2  1  2  4  8                                      ginosa                                                                        Bac. fragilis                                                                        ES 25                                                                              16 0.5                                                                              0.125                                                                            0.125                                                                            0.25                                                                             1  0.125                                                                            1  0.125                                                                            4                                      ID.sub.50 (μg/ml)                                                                      24 1  4  8  10 1  4  16 10 8                                      __________________________________________________________________________

                  TABLE 2                                                         ______________________________________                                        MIC values (μg/ml) and ID.sub.50 values of active compounds                from the prior art                                                                           Examples from EP 520 240                                                            35            36    7                                    Species   Strain     Ref. 1  Ref. 2                                                                              Ref. 3                                                                              Ref. 4                               ______________________________________                                        E. coli   Neumann    0.015   0.015 0.015 0.03                                 Staph. aureus                                                                           133        0.015   0.015 0.015 0.015                                Staph. aureus                                                                           ICB 25701  0.06    0.015 0.015 --                                   Ps. aerugiosa                                                                           Walter     0.5     1     0.5   1                                    Bac. fragilis                                                                           ES 25      0.5     0.25  0.125 0.5                                  ID.sub.50 (μg/ml)                                                                    0.015      0.1     0.1   0.1                                        ______________________________________                                         Ref. 1:                                                                       7(4-amino-7-methyl-1,3,3a,4,7,7a-hexahydro-isoindol-2-yl)-1-cyclopropyl-6    8-difluoro-1,4-dihydro-4-oxo-3-quinolinecaboxylic acid,                        Ref. 2:                                                                       7(4-amino-7-methyl-1,3,3a,4,7,7a-hexahydro-isoindol-2-yl)-1-cyclopropyl-6    fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid,                 Ref. 3:                                                                       7(4-amino-7-methyl-1,3;3a,4,7,7a-hexahydro-isoindol-2-yl)-8-chloro-1-cycl    propyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid,                  Ref. 4:                                                                       7(7-methyl-4-methylamino-1,3,3a,4,7,7a-hexahydro-isoindol-2-yl)-8-chloro-    -cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid.       

Preparation of the intermediate products

EXAMPLE Z 1

A. 1-Methoxy-4-azatricyclo 5.2.2.0²,6 !undec-8-en-3,5-dione

11 g (0.1 mol) of 1-methoxycyclohexa-1,4-diene are heated under refluxwith 0.1 g of tris(triphenylphosphine)-ruthenium dichloride and 8.8 g(0.09 mol) of maleimide in 100 ml of absolute chloroform overnight. Themixture is concentrated and the residue is recrystallized from 100 ml oftoluene.

Yield: 17.6 g (84.9% of theory), Melting point: 159°-161° C.

B. 1-Methoxy-4-azatricyclo 5.2.2.0²,6 !undec-8-ene

20.5 g (0.1 mol) of 1-methoxy-4azatricyclo 5.2.2.0²,6!undec-8-ene-3,5-dione in 100 ml of absolute tetrahydrofuran are addeddropwise to 6 g of LiAlH₄ in 200 ml of absolute tetrahydrofuran and themixture is stirred under reflux overnight. 6 ml each of water, 15%strength KOH solution and water again are added, the inorganic salts arefiltered off with suction and boiled out twice with tetrahydrofuran, thefiltrates are concentrated and the residue is distilled.

Yield: 12.3 g (68.6% of theory) Boiling point: 100° C./0.04 mbar.

EXAMPLE Z 2

A. 1-Ethoxycarbonyl-4-azatricyclo 5.2.2.0²,6 !undec-8-ene-3,5-dione

13.5 g (0.138 mol) of maleimide and 25.3 g (0.17 mol) of ethyl1,3-cyclohexadiene-1-carboxylate are heated under reflux with 1.4 g of4-(tert-butyl)-pyrocatechol in 275 ml of toluene overnight The mixtureis concentrated and the residue is recrystallized from isopropanol.

Yield: 25.9 g (75% of theory) Melting point: 172°-173° C.

B. 1-Hydroxymethyl-4-azatricyclo 5.2.2.0- 5.2.2.0²,6 !undec-8-ene

12.5 g (50 mmol) of 1-ethoxycarbonyl-4-azatricyclo- 5.2.2.0²,6!undec-8-ene-3,5-dione are reduced with LiAlH₄ as described under Z 1-Band the mixture is worked up accordingly.

Yield: 2.3 g (25.6% of theory) Boiling point: 122°-124° C./0.5 mbar.

EXAMPLE Z 3

A. 1-Dimethylamino-4-azatricyclo 5.2.2.0².6 !undec-8-ene-3,5-dione

9 g (73 mmol) of 1-dimethylaminocyclohexa-1,3-diene and 6.4 g (66 mmol)of maleimide are stirred in 100 ml of absolute dioxane at roomtemperature overnight. The mixture is concentrated and the residue isrecrystallized from isopropanol.

Yield: 12 g (82.5% of theory) Melting point: 170°-172° C.

B. 1-Dimethylamino-4-azatricyclo 5.2.2.0²,6 !undec-8-ene

12 g (54.5 mmol) of 1-diethylamino-4-azatricyclo- 5.2.2.0²,6!undec-8-ene-3,5-dione are reduced with LiAlH₄ as described under Z 1-Band the mixture is worked up accordingly.

Yield: 7.5 g (71.5% of theory) Boiling point: 91°-93° C./0.04 mbar.

EXAMPLE Z 4

A. 1-Cyano-4-azatricyclo 5.2.2.0²,6 !undec-8-ene-3,5-dione

59 g (0.56 mol) of 1-cyano-cyclohexa-1,3-diene are heated at 150° C.with 54 g (0.56 mol) of maleimide and 5 g of 4-(tert-butyl)-pyrocatecholin 1000 ml of dimethylformamide for 8 hours. The mixture is concentratedthe residue is stirred with water and toluene and the product which hascrystallized is filtered off with suction, washed with isopropanol anddried in air.

Yield: 71 g (67.5% of theory) Melting point: 213° C.

B. 1-Aninomethyl-4-azatricyclo 5.2.2.0²,6 !undec-8-ene

15.4 g (76.2 mmol) of 1-cyano-4-azatricyclo 5.2.2.0²,6!undec-8-ene-3,5-dione are reduced with LiAlH₄ as described under Z 1-Band the mixture is worked up accordingly.

Yield: 7 g (51.5% of theory) Boiling point: 97° C./0.1 mbar.

EXAMPLE Z 5

A. 4-Azatricyclo 5.2.2.0²,6 !undec-8ene-3,5-dione-1-carboxylic acidamide

41 g (0.203 mol) of 1-cyano-4-azatricyclo 5.2.2.0²,6!undec-8-ene-3,5-dione are dissolved in 150 ml of 10% strength sodiumhydroxide solution, and 130 ml of 30% strength H₂ O₂ are added dropwiseat 0° C. The mixture is stirred at 0° C. for 30 minutes and then at roomtemperature for 3 hours, the pH is brought to 4.5 with acetic acid andthe product which crystallizes out is filtered off with suction.

Yield: 36.3 g (81% of theory) Melting point: 158° C. (from isopropanol).

B. 1Amino-4-azatricyclo 5.2.2.0²,6 !undec-8-ene-3,5-dione

74.5 g (0.338 mol) of 4-azatricyclo 5.2.2.0²,6!undec-8-ene-3,5-dione-1-carboxylic acid amide are heated under refluxwith 139 g (0.354 mol) of I-hydroxy-I-tosyloxy-iodobenzene in 1000 ml ofacetonitrile for 3 hours. The mixture is cooled and the toluenesulphonicacid salt of the product which has crystallized out is filtered off withsuction.

Yield: 112 g (95% of theory) Melting point: 255°-256° C.

The salt is suspended in 300 ml of water, and a solution of 12.5 g ofNaOH in 40 ml of water is added The salt dissolves rapidly, and aftersome time the product crystallizes out.

Yield: 43.5 g (70% of theory).

C. 1-Amino-4-cyclo 5.2.2.0²,6 !undec-8-ene

45 g (0.234 mol) of 1-amino-4-azatricyclo 5.2.2.0²,6!undec-8-ene-3,5-dione are reduced with 24 g of LiAlH₄ in 500 ml ofabsolute dioxane as under Z 1-B and the mixture is worked upaccordingly.

Yield: 14.8 g (40% of theory) Boiling point: 95°-105° C./0.08 mbar.

EXAMPLE Z 6

A. 4-Benzyl-1-cyano-4-azatricyclo 5.2.2.0²,6 !undec-8-ene-3,5-dione

39 g (0.35 mol) of 1-cyano-cyclohexa-1,3-diene are heated at 100° C.with 65.5 g (0.35 mol) of N-benzyl-maleimide in 700 ml of xylene for onehour and then under reflux for 1 hour. After cooling, the crystals arefiltered off with suction and recrystallized from xylene.

Yield: 75 g (73.3% of theory) Melting point: 175°-177° C.

B. 1-Aminomethyl-4-benzyl-4-azatricyclo 5.2.2.0²,6 !undec-8-ene

14.6 g (50 mmol) of 4benzyl-1-cyano-4-azatricyclo 5.2.2.0²,6!undec-8-ene-3,5-dione are reduced with 5 g of LiAlH₄ as described underZ 1-B and the mixture is worked up accordingly.

Yield: 6.4 g (47.7% of theory) Boiling point: 158° C./0.1 mbar.

C. 1-Aminomethyl-4-azatricyclo 5.2.2.0²,6 !undecane

7.4 g (27.5 mmol) of 1-aminomethyl-4-benzyl-4-azatricyclo 5.2.2.0²,6!undec-8-ene are hydrogenated in 100 ml of tetrahydrofuran using 1.5 gof palladium/active charcoal at 100° C./100 bar. The catalyst isfiltered off with suction and the residue is distilled.

Yield. 3.1 g (62.5% of theory) Boiling point: 89° C./0.1 mbar.

EXAMPLE Z 7

A. 4-Benzyl-4-azatricyclo 5.2.2.0²,6!undec-8-ene-3,5-dione-1-carboxamide

14.5 g (50 mmol) of 4benzyl-1-cyano-4-azatricyclo 5.2.2.0²,6!undec-8-ene-3,5-dione are dissolved in 25 ml of methylene chloride, 2.5g of tetrabutylammonium hydrogen sulphate and 17.5 ml of 20% strengthsodium hydroxide solution are added, and 24 ml of 30% strength H₂ O₂ areadded dropwise at 0° C. The mixture is stirred at 0° C. for 30 minutesand then overnight at room temperature and diluted with methylenechloride, and the organic phase is separated off and washed with sodiumchloride solution. It is dried over MgSO₄ and concentrated and thecrystalline product is boiled up with xylene, any unreacted startingmaterial dissolving. The product is filtered off hot with suction anddried in air.

Yield: 13 g (83.8% of theory) Melting point: 224° C.

B. 1-Amino-4benzyl-4-azatricyclo 5.2.2.0²,6 !undec-8-ene-3,5-dione

17.6 g (56.7 mmol) of 4-benzyl-4-azatricyclo 5.2.2.²,6!undec-8-ene-3,5-dione-1-carboxamide are reacted with 22.2 g ofI-hydroxy-I-tosyloxy-iodobenzene as described under Z 5-B and the mireis worked up accordingly.

Yield: 22.5 g (87% of theory) of the tosylate Melting point: 222° C.

The free base is prepared from this as described under Z 5-B.

Yield: 12 g (86% of theory) Melting point: 130°-134° C.

C. 1-Amino-4-benzyl-4-azatricyclo 5.2.2.0²,6 !undec-8-ene

19.3 g (68.2 mmol) of 1-amino-4-benzyl-4-azatricyclo 5.2.2.²,6!undec-8-ene-3,5-dione are reduced with 8 g of LiAlH₄ as described underZ 1-B and the mixture is worked up accordingly.

Yield: 12.6 g (72.6% of theory) Boiling point: 145°-148° C./0.15 mbarMelting point: 59°-61° C.

D. 1-Amino-4-azatricyclo 5.2.2.0²,6 !undecane

8.3 g (32.6 mmol) of 1-amino-4-benzyl-4-azatricyclo 5.2.2.0²,6!undec-8-ene are hydrogenated in 100 ml of ethanol over 1 g ofpalladium/active charcoal at 100° C./100 bar. The catalyst is filteredoff with suction, the filtrate is concentrated and the residue isdistilled.

Yield: 4.4 g (81.2% of theory) Boiling point: 115° C./0.05 mbar.

EXAMPLE Z 8

A. Ethyl 4-benzyl-3,5-dioxo-4-azatricyclo 5.2.1.0²,6!dec-8-ene-1-carboxylate

32.8 g (0.17 mol) of N-benzylmaleimide are heated under reflux with 24.2g (0.17 mol) of diethyl tricyclo 5.2.1.0²,6!deca-3,8-diene-1,4-dicarboxylate in 200 ml of 1,4-dioxane overnight.The mixture is concentrated, the residue is taken up in 80 ml ofisopropanol and the product is allowed to crystallize out.

Yield: 23 g (41.6% of theory) Melting point: 78°-80° C.

B. 4-Benzyl-3,5-dioxo-4-azatricyclo 5.2.1.0²,6 !dec-8-ene-1-carboxylicacid

30 g (90 mmol) of ethyl 4benzyl-3,5-dioxo-4-azatricyclo 5.2.1.0²,6!dec-8-ene-1-carboxylate are heated under reflux with 5.3 g (0.13 mol)of NaOH in 150 ml of methanol overnight. The mixture is concentrated,the residue is taken up in 150 ml of water and the mixture is acidifiedwith hydrochloric acid. The product which crystallizes out is filteredoff with suction, washed with water and dried in air.

Yield: 23.5 g (87.8% of theory) Melting point: 157° C.

C. 4-Benzyl-3,5-dioxo-4-azatricyclo 5.2.1.0²,6 !dec-8-ene-1-carboxylicacid amide

1.1 g (11 mmol) of triethylamine and then 1.15 g (12 mmol) of methylchloroformate are added dropwise to 3 g (10 mmol) of4-benzyl-3,5-dioxo-4-azatricyclo 5.2.1.0²,6 !dec-8-ene-1-carboxylic acidin 20 ml of absolute tetrahydrofuran at 0° C. The mixture is stirred at0° C. for a further hour and the solution is poured onto 20 ml ofammonia solution. The mixture is stirred at room temperature for 1 hourand extracted several times with chloroform, and the extracts are driedover MgSO₄ and concentrated, whereupon the product crystallizes.

Yield: 1.78 g (60% of theory) Melting point: 168° C.

Preparation of the active compounds

EXAMPLE 1 ##STR14##

265 mg (1 mmol) of1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acidare heated under reflux in a mixture of 4 ml of acetonitrile and 2 ml ofdimethylformamide with 170 mg (1.5 mmol) of 1,4-diazabicyclo2.2.2!octane and 210 mg (1.1 mmol) of 86% pure 4-aza-tricyclo 5.2.2.0²,6!undec-8-en-1-ylamine for 1 hour. The mixture is concentrated, theresidue is stirred with 40 ml of water (pH=7) and the precipitate whichhas separated out is filtered off with suction, washed with water anddried at 80° C. under a high vacuum.

Yield: 286 mg (70% of theory) of 7-(1-amino-4-aza-tricyclo 5.2.2.0²,6!undec-8-en-4-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid, Melting point: 272°-274° C. (with decomposition).

EXAMPLE 2 ##STR15##

Under conditions corresponding to those in Example 1,1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid gives 7-(1-amino-4-aza-tricyclo 5.2.2.0²,6!undec-8-en-4-yl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid in a 61% yield,

Melting point: 226°-227° C. (with decomposition).

EXAMPLE 3 ##STR16##

Under conditions corresponding to those in Example 1,8-chloro-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid gives a crude product which is purified by chromatography oversilica gel (mobile phase: methylene chloride/17% strength aqueousammonia/methanol 30:8:1). 7-(1-Amino-4-aza-tricyclo 5.2.2.0²,6!undec-8-en-4-yl)-8-chloro-1-cyclopropyl-6-fluoro-1,4dihydro-4-oxo-3-quinolinecarboxylicacid is obtained in a yield of 72%,

Melting point: 218°-229° C. (with decomposition).

EXAMPLE 4 ##STR17##

Under conditions corresponding to those in Example 1,1-ethyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid givesa crude product which is purified by chromatography over silica gel(mobile phase: methylene chloride/17% strength aqueous ammonia/methanol30:8:1). 7-(1-Amino-4-aza-tricyclo 5.2.2.0²,6!undec-8-en-4-yl)-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid, the melting point of which cannot be determined (sintering from75° C.) is isolated in a yield of 53%.

¹ H-NMR (CF₃ COOD): δ 6.41 d (1 H) and 6.63 ppm "t" (1 H).

EXAMPLE 5 ##STR18##

Under conditions corresponding to those in Example 1,1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylicacid gives 7-(1-amino-4-aza-tricyclo 5.2.2.0²,6!undec-8-en-4-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylicacid in a yield of 64%,

Melting point: 224°-225° C. (with decomposition).

EXAMPLE 6 ##STR19##

Under conditions corresponding to those in Example 1,1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-8-trifluoromethyl-3-quinolinecarboxylicacid gives a crude product which is purified by chromatography oversilica gel (mobile phase: methylene chloride/17% strength aqueousammonia/methanol 30:8:1). 7-(1-Amino-4-aza-tricyclo 5.2.2.0²,6!undec-8-en-4-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-8-trifluoromethyl-3-quinolinecarboxylicacid is isolated in a yield of 32%,

Melting point: 163°-166° C. (with decomposition).

EXAMPLE 7 ##STR20##

Under conditions corresponding to those in Example 1,1-cyclopropyl-8-ethinyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid gives 7-(1-amino-4-aza-tricyclo 5.2.2.0²,6!undec-8-en-4-yl)-1-cyclopropyl-8-ethinyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid, the melting point of which cannot be determined because ofpremature sintering from 107° C., in a yield of 87%.

¹ H-NMR (CDCl₃): δ 3.84 s (1 H), 6.03 d (1 H), 6.20 ppm dd (1 H).

EXAMPLE 8 ##STR21##

Under conditions corresponding to those in Example 1,6,7,8-trifluoro-1-(cis-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid gives a crude product which is purified by chromatography oversilica gel (mobile phase: methylene chloride(17% strength aqueousammonia/methanol 30:8:1). 7-(1-Amino-4-aza-tricyclo 5.2.2.0²,6!undec-8-en-4-yl)-6,8-difluoro-1-(cis-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid is isolated in a yield of 55%,

Melting point: 222°-225° C. (with decomposition).

EXAMPLE 9 ##STR22##

150 mg (0.53 mmol) of 9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido1,2,3-d,e! 1,3,4!-benzoxadiazine-6-carboxylic acid are heated at 110° C.with 130 mg (0.79 mmol) of 4-azatricyclo 5.2.2.0²,6 !undec-8en-1-ylaminein 5 ml of pyridine under argon for 8 hours. The mixture is concentratedunder a high vacuum and the residue is recrystallized from ethanol anddried.

Yield: 55 mg (24% of theory) of 10-(1-amino-4-azatricyclo 5.2.2.0²,6!undec-8-en-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido1,2,3-d,e! 1,3,4!benzoxadiazine-6-carboxylic acid,

Melting point: 215°-223° C. (with decomposition).

EXAMPLE 10 ##STR23##

150 mg (0.51 mmol) of8-amino-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido 1,2,3-d,e!1,3,4!benzoxadiazine-6-carboxylic acid are heated at 120° C. with 125 mg(0.76 mmol) of 4-azatricyclo 5.2.2.0²,6 !undec-8-en-1-ylamine in 4.5 mlof dimethyl sulphoxide under argon for three hours. The mixture isconcentrated under a high vacuum and the residue is recrystallized fromethanol and dried.

Yield: 190 mg (85% of theory) of 8-amino-10-(1-amino-azatricyclo5.2.2.0²,6!-undec-8-en-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido1,2,3-d,e!- 1,3,4!benzoxadiazine-6-carboxylic acid,

Melting point: 230°-239° C. (with decomposition).

EXAMPLE 11 ##STR24##

350 mg (1.086 mmol) of 7,8-difluoro-5-oxo-9,1-N-methylimino)methano!-5H-thiazolo- 3,2-a!-quinoline-4-carboxylic acidare heated at 120° C. with 267 mg (1.63 mmol) of 4-azatricyclo5.2.2.0²,6 !undec-8-en-1-ylamine in 8 ml of dimethyl sulphoxide underargon for six hours. The mixture is concentrated under a high vacuum andthe residue is recrystallized from ethanol and dried.

Yield: 330 mg (65% of theory) of 8-(1-amino-4-azatricyclo 5.2.2.0²,6!undec-8-en-4-yl)-7-fluoro-5-oxo-9,1-(N-methyl-imino)methano!-5H-thiazolo 3,2-a!quinoline-4-carboxylic acid,

Melting point: >300° C.

EXAMPLE 12 ##STR25##

Analogously to Example 11, reaction with 7,8-difluoro-5-oxo-9,1-(N-ethylimino)methano!-5H-thiazolo 3,2-a!quinoline-4-carboxylic acidgives 8-(1-amino-4-azatricyclo 5.2.2.0²,6!undec-8-en-4-yl)-7-fluoro-5-oxo-9,1-(N-ethyl-imino)methano!-5H-thiazolo3,2-a!quinoline-4-carboxylic acid.

Melting point: >300° C.

EXAMPLE 13 ##STR26##

100 mg (0.323 mmol) of 7,8-difluoro-5-oxo-9,1-(epoxymethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid are heated at 100° C. with 80 mg (0.49mmol) of 4-azatricyclo 5.2.2.0²,6 !undec-8-en-1-ylamine in 3 ml of DMSOunder argon for 2 hours. The mixture is concentrated under a high vacuumand the residue is recrystallized from ethanol and dried.

Yield: 114 mg (78% of theory) of 8-(1-amino-4-azatricyclo 5.2.2.0²,6!undec-8-en-4-yl)-7-fluoro-5-oxo-9,1-(epoxymethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid,

Melting point: 254°-263° C.

EXAMPLE 14 ##STR27##

100 mg (0.307 mmol) of7,8-difluoro-5-oxo-9,1-(epithiomethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid are heated at 120° C. with 76 mg (0.46mmol) of 1-amino-4-azatricyclo 5.2.2.0²,6 !undec-8-ene in 3 ml of DMSOunder argon for four hours. The mixture is concentrated under a highvacuum and the residue is recrystallized from ethanol and dried.

Yield: 119 mg (83% of theory) of 8-(1-amino-4-azatricyclo 5.2.2.0²,6!undec-8-en-4-yl)-7-fluoro-5-oxo-9,1-(epithiomethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid,

Melting point: 285°-290° C.

EXAMPLE 15 ##STR28##

80 mg (0.254 mmol) of 7,8-difluoro-1-methyl-5-oxo-5H-thiazolo3,2-a!-quinoline-4-carboxylic acid are heated at 80° C. with 46 mg (0.28mmol) of 4-azatricyclo 5.2.2.0²,6 !undec-8en-1-ylamine in 3 ml of DMSOunder argon for 3 hours. The mixture is concentrated under a high vacuumand the residue is recrystallized from ethanol and dried.

Yield: 41 mg (35% of theory) of 8-(1-amino-4-azatricyclo 5.2.2.0²,6!-undec-8en-4-yl)-7-fluoro-1-methyl-5-oxo-5H-thiazolo3,2-a!-quinoline-4-carboxylic acid,

Melting point: 122° C.

EXAMPLE 16 ##STR29##

283 mg (1 mmol) of1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid are heated under reflux in a mixture of 2 ml of acetonitrile and 1ml of dimethylformamide with 224 mg (2 mmol) of 1,4-diazabicyclo2.2.2!octane and 210 mg (1.1 mmol) of (4-azatricyclo 5.2.2.0²,6!undec-8-en-1-yl)-dimethylamine for 1 hour. The mixture is concentrated,the residue is stirred with water and the precipitate which hasseparated out is filtered off with suction, washed with water and driedat 100° C. under a high vacuum.

Yield: 360 mg (79% of theory) of1-cyclopropyl-7-(1-dimethylamino-4-azatricyclo 5.2.2.0²,6!undec-8-en-4-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,

Melting point: 238°-240° C. (with decomposition).

EXAMPLE 17 ##STR30##

Under conditions corresponding to those in Example 16,8-chloro-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid gives 8-chloro-1-cyclopropyl-7-(1-dimethylamino-4-azatricyclo5.2.2.0²,6!undec-8-en-4-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acidin a yield of 65%,

Melting point: 180°-183° C. (with decomposition).

EXAMPLE 18 ##STR31##

283 mg (1 mmol) of1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid are heated under reflux in a mixture of 4 ml of acetonitrile and 2ml of dimethylformamide with 224 mg (2 mmol) of 1,4-diazabicyclo2.2.2!octane and 191 mg (1.1 mmol) of 4-azatricyclo 5.2.2.0²,6!undec-1-ylamine for 1 hour. The m is concentrated at 70° C./15 mbar,the residue is stirred with water and the precipitate which hasseparated out is filtered off with suction, washed with water and driedat 100° C. under a high vacuum.

Yield: 303 mg (73% of theory) of 7-(1-amino-4-azatricyclo 5.2.2.0².6!undec-4-yl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid,

Melting point: 240°-245° C. (with decomposition).

EXAMPLE 19 ##STR32##

Under conditions corresponding to those in Example 18,8-chloro-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid gives 7-(1-amino-4-azatricyclo 5.2.2.0²,6!undec-4-yl)-8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid in a yield of 93%,

Melting point: 232°-235° C. (with decomposition).

EXAMPLE 20 ##STR33##

208 mg (2 mmol) of trimethyl borate, 123 mg (1.1 mmol) of1,4-diazabicyclo 2.2.2!octane and 185 mg (1.1 mmol) of 4-aza-tricyclo5.2.2.0²,6 !undec-1-ylamine are added to 295 mg (1 mmol) of1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylicacid in 3 ml of acetonitrile at room temperature and the mixture is thenheated under reflux for 4 hours. The reaction mixture is concentrated at80° C./20 mbar, the residue is stirred with water and the precipitatewhich has separated out is filtered off with suction, washed with waterand dried at 100° C. under a high vacuum.

Yield: 218 mg (51% of theory) of 7-(1-amino-4-azatricyclo 5.2.2.0²,6!undec-4-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylicacid,

Melting point: 234°-237° C. (with decomposition).

EXAMPLE 21 ##STR34##

Under conditions corresponding to those in Example 18,1-cyclopropyl-6,7-fluoro-1,4-dihydro-4-oxo-8-trifluoromethyl-3-quinolinecarboxylicacid gives a crude product, from which 7-(1-amino-4-azatricyclo5.2.2.0²,6!undec-4-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-8-trifluoromethyl-3-quinolinecarboxylicacid was isolated in a yield of 34% after purification by chromatographyover silica gel (mobile phase: methylene chloride/17% strength aqueousammonia/methanol 30:8:1).

Melting point: 211°-215° C. (with decomposition).

EXAMPLE 22 ##STR35##

100 mg (0.336 mmol) of8-amino-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido 1,2,3-d,e!1,3,4!benzoxadiazine-6-carboxylic acid are heated at 120° C. with 111 mg(0.67 mmol) of 4-azatricyclo 5.2.2.0²,6 !undecan-1-ylamine in 3 ml ofdimethyl sulphoxide under argon for 4 hours. The mixture is concentratedunder a high vacuum and the residue is recrystallized from ethanol anddried.

Yield: 105 mg (70% of theory) of 8-amino-10-(1-amino-4-azatricyclo5.2.2.0²,6 !undecan-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido1,2,3-d,e! 1,3,4!benzoxadiazine-6-carboxylic acid,

Melting point 236° C.

EXAMPLE 23 ##STR36##

Analogously to Example 22, reaction with9,10difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido 1,2,3-d,e!1,3,4!benzoxadiazine-6-carboxylic acid gives 10-(1-amino-4-azatricyclo5.2.2.0²,6 !undecan-4-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido1,2,3-d,e! 1,3,4!benzoxadiazine-6-carboxylic acid.

Melting point: 143° C.

EXAMPLE 24 ##STR37##

150 mg (0.465 mmol) of 7,8-difluoro-5-oxo-9,1-(N-methylimino)methano!-5H-thiazolo 3,2-a!quinoline-4-carboxylic acidare heated at 130° C. with 153 mg (0.92 mmol) of 4-aza-tricyclo5.2.2.0²,6 !undecan-1-yl in 3 ml of dimethyl sulphoxide under argon for3 hours. The mixture is concentrated under a high vacuum and the residueis recrystallized from ethanol and dried.

Yield: 137 mg (63% of theory) of 8-(1-amino-4-azatricyclo 5.2.2.0²,6!undecan-4-yl)-7-fluoro-5-oxo-9,1- N-methyl-imino)methano!-5H-thiazolo3,2-a!quinoline-4-carboxylic acid,

Melting point: >300° C.

EXAMPLE 25 ##STR38##

Analogously to Example 13, reaction with 1-amino-4-azatricyclo5.2.2.0²,6 !undecane gives 8-(1-amino-4-azatricyclo 5.2.2.0²,6!undecan-4-yl)-7-fluoro-5-oxo-9,1-(epoxymethino)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid.

Melting point: 270° C.

EXAMPLE 26 ##STR39##

Analogously to Example 14, reaction with 1-amino-4-azatricyclo5.2.2.0²,6 !undecane gives 8-(1-amino-4-azatricyclo 5.2.2.0²,6!undecan-4-yl)-7-fluoro-5-oxo-9,1-(epithiomethano)-5H-thiazolo3,2-a!quinoline-4-carboxylic acid.

Melting point: 270° C. (with decomposition).

EXAMPLE 27 ##STR40##

283 mg (1 mmol) of1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid are heated under reflux in a mixture of 4 ml of acetonitrile and 2ml of dimethylformamide with 224 mg (2 mmol) of 1,4-diazabicyclo2.2.2!octane and 200 mg (1.1 mmol) of (4-azatricyclo 5.2.2.0²,6!undec-8-en-1-yl)-methanol for 1 hour. The precipitate which hasseparated out is filtered off with suction, washed with water and driedat 80° C. under a high vacuum.

Yield: 360 mg (81% of theory) of1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(1-hydroxymethyl-4-azatricyclo5.2.2.0²,6 !undec-8-en-4-yl)-4-oxo-3-quinolinecarboxylic acid,

Melting point: 242°-244° C. (with decomposition).

EXAMPLE 28 ##STR41##

566 mg (2 mmol) of1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid are heated under reflux in a mixture of 8 ml of acetonitrile and 4ml of dimethylformamide with 350 mg (3.1 mmol) of 1,4-diazabicyclo2.2.2!octane and 380 mg (2.1 mmol) of 1-methoxy-4aza-tricyclo 5.2.2.0²,6!undec-8-ene for 1 hour. The mixture is concentrated, the residue isstirred with 10 ml of water (pH=7) and the precipitate which hasseparated out is filtered off with suction, washed with water and driedat 90° C. under a high vacuum. 821 mg of a crude product which isrecrystallized from glycol monomethyl ether, washed with ethanol anddried at 120° C. under a high vacuum are obtained.

Yield: 676 mg (76% of theory) of1-cyclopropyl-6,8-difluoro-1,4dihydro-7-(1-methoxy-4-azatricyclo5.2.2.0.sup.2,6 !undec-8-en-4-yl)-4-oxo-3-quinolinecarboxylic acid,

Melting point: 183°-185° C. (with decomposition).

EXAMPLE 29 ##STR42##

Under conditions corresponding to those in Example 18, (4-azatricyclo5.2.2.0²,6 !undec-8-en-1-ylmethyl)amine gives, after recrystallizationfrom glycol monomethyl ether, 7-(1-aminomethyl-4-azatricyclo 5.2.2.0²,6!undec-8-en-4-yl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid in a yield of 59%,

Melting point: 238°-240° C. (with decomposition).

EXAMPLE 30 ##STR43##

In accordance with Example 1,8-cyano-1-cyclopropyl-7-chloro-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid is employed and the mixture is heated at 80° C. for 8 hours. Afterconcentration and working up with ethanol, 7-(1-amino-4-azatricyclo5.2.2.0²,6!undec-8-en-4-yl)-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid is obtained in a yield of 51%, Melting point: 180°-182° C. (withdecomposition).

EXAMPLE 31 ##STR44##

290 mg (≈1.5 mmol) of 86% pure 4-aza-tricyclo 5.2.2.0²,6!undec-8-en-1-ylamine are added to 283 mg (1 mmol) of7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid in 6 ml of acetonitrile at 25° C. and the mixture is stirred at 25°C. for 1 hour. The precipitate is filtered off with suction, washed withethanol, dried at 60° C./0.1 mbar (crude yield: 398 mg) and purified bychromatography (silica gel, methylene chloride/17% strength aqueousammonia/methanol 30:8:1).

Yield: 171 mg (42% of theory) of 7-(1-amino-4-azatricyclo 5.2.2.0²,6!undec-8-en-4-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid,

Melting point: 308°-311° C. (with decomposition).

EXAMPLE 32 ##STR45## A. Analogously to Example 31, the reaction iscarried out with ethyl7-chloro-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylateto give ethyl 7-(1-amino-4-azatricyclo 5.2.2.0²,6!undec-8-en-4-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylatein a yield of 41%,

Melting point: 210°-213° C. (with decomposition).

B. 170 mg (0.33 mmol) of ethyl 7-(1-amino-4-azatricyclo 5.2.2.0²,6!undec-8-en-4-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylateare heated under reflux in a mixture of 2 ml of acetic acid and 1.5 mlof half-concentrated hydrochloric acid for 2 hours. The solution isconcentrated, the residue is stirred with a little water and theprecipitate is filtered off with suction.

Yield: 150 mg (92% of theory) of 7-(1-amino-4-azatricyclo 5.2.2.0²,6!undec-8-en-4-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid hydrochloride,

Melting point: 270°-272° C. (with decomposition).

EXAMPLE 33

Under conditions corresponding to those in Example 1,6,7-difluoro-1-(2,4-difluorophenyl)-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylicacid gives a crude product which is purified by chromatography on silicagel (mobile phase: methylene chloride/17% strength aqueousammonia/methanol 30:8:1). 7-(1-Amino-4-azatricyclo 5.2.2.0²,6!undec-8-en-4-yl)-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylicacid is isolated in a yield of 91%,

Melting point: 281°-283° C. (with decomposition).

EXAMPLE 34 ##STR46##

Under conditions corresponding to those in Example 1,1-tert-butyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acidgives 7-(1-amino-4-aza-tricyclo 5.2.2.0²,6!undec-8-en-4-yl)-1-tert-butyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid in a yield of 61%,

Melting point: 263°-265° C. (with decomposition).

We claim:
 1. A compound of the formula (I)

    T--Q                                                       (I)

in which Q denotes a radical of the formulae ##STR47## wherein R¹represents alkyl which has 1 to 4 carbon atoms and is optionally mono-or disubstituted by halogen or hydroxyl, alkenyl having 2 to 4 carbonatoms, cycloalkyl which has 3 to 6 carbon atoms and is optionallysubstituted by 1 or 2 fluorine atoms, bicyclo 1.1.1!-pent-1-yl,1,1-dimethylpropargyl, 3-oxetanyl, methoxy, amino, methylamino,dimethylamino or phenyl which is optionally mono- or disubstituted byhalogen, amino or hydroxyl, R² represents hydrogen, alkyl which has 1 to3 carbon atoms and is optionally substituted by hydroxyl, methoxy, aminoor dimethylamino, benzyl, (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl,acetoxymethyl, pivaloyloxymethyl, 5-indanyl, phthalidinyl or3-acetoxy-2-oxo-butyl, X¹ represents halogen or nitro, X² representshydrogen, halogen, amino, hydroxyl, methoxy, mercapto, methyl,halogenomethyl or vinyl, A represents NT denotes a radical of theformula ##STR48## wherein B represents NR³ R⁴ or OR⁵, wherein R³represents hydrogen, methyl or alkoxycarbonyl having 1 to 4 carbon atomsin the alkyl part, R⁴ represents hydrogen or methyl and R⁵ representshydrogen or methyl, R⁶ represents hydrogen or methyl, m represents 0 or1 and n represents 1 or 2,and wherein a single or a double bond canstand between the carbon atoms a and b, or pharmaceutically usablehydrate or acid addition salt thereof, or an alkali metal, alkalineearth metal, silver or guanidinium salt of an underlying carboxylicacid.
 2. A compound of the formula (I) according to claim 1,in which Qand T have the abovementioned meaning and R¹ represents alkyl which has1 to 4 carbon atoms and is optionally mono- or disubstituted by halogen,alkenyl having 2 to 3 carbon atoms, cycloalkyl which has 3 or 4 carbonatoms and is optionally substituted by 1 fluorine atom, bicyclo1.1.1!pent-1-yl, 1,1-dimethylpropargyl, 3-oxetanyl, methylamino orphenyl which is optionally mono- or disubstituted by fluorine, amino orhydroxyl, R² represents hydrogen, alkyl having 1 to 2 carbon atoms,benzyl or (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl, X¹ representsfluorine or chlorine, X² represents hydrogen, halogen, amino, methyl,trifluoromethyl or vinyl, A represents N B represents NR³ R⁴ or OR⁵,whereinR³ represents hydrogen, methyl or alkoxycarbonyl having 1 to 4carbon atoms in the alkyl part, R⁴ represents hydrogen or methyl and R⁵represents hydrogen or methyl, R⁶ represents hydrogen or methyl, mrepresents 0 or 1 and n represents 1 or 2,wherein a single or a doublebond can stand between the carbon atoms a and b, or a pharmaceuticallyusable hydrate or acid addition salt thereof or an alkali metal,alkaline earth metal, silver or guanidinium salt of an underlyingcarboxylic acid.
 3. A compound of the formula (I) according to claim1,in which Q and T have the abovementioned meaning and in which R¹represents alkyl which has 1 to 4 carbon atoms and is optionally mono-or disubstituted by fluorine, vinyl, cyclopropyl which is optionallysubstituted by 1 fluorine atom or phenyl which is optionally mono- ordisubstituted by fluorine, R² represents hydrogen, alkyl having 1 to 2carbon atoms or (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl, X¹ representsfluorine, X² represents hydrogen, fluorine, amino, methyl or vinyl, Arepresents N B represents NR³ R⁴ or OR⁵, whereinR³ represents hydrogenor methyl, R⁴ represents hydrogen or methyl and R⁵ represents hydrogenor methyl, R⁶ represents hydrogen, m represents 0 or 1 and n represents1 or 2,wherein a single or a double bond can stand between the carbonatoms a and b, or a pharmaceutically usable hydrate or acid additionsalt thereof or an alkali metal, alkaline earth metal, silver orguanidinium salt of an underlying carboxylic acid.
 4. Diastereomericallypure and enantiomerically pure compounds according to claim
 1. 5. Anantibacterial composition comprising an antibacterially effective amountof a compound or addition product thereof according to claim 1 and adiluent.
 6. A composition according to claim 5 in the form of a tablet,capsule or ampule.
 7. A composition according to claim 5, wherein thediluent comprises an animal feed stock.
 8. A method of combatingbacteria in a patient in need thereof which comprises administering tosuch patient an antibacterially effective amount of a compound oraddition product thereof according to claim
 1. 9. A method of promotingthe growth of an animal which comprises administering to said animal agrowth promoting effective amount of a compound or addition productthereof according to claim 1.